Alnylam Aces Phase III Cardio Trial, Eyes Label Expansion for RNAi Therapy

Cambridge, MA, USA - June 28, 2022: Exterior view of the Alnylam headquarters in Cambridge, Massachusetts. Alnylam Pharmaceuticals, Inc. is an American biotechnology company focused on the discovery, development and commercialization of RNA interference (RNAi) therapeutics for genetically defined diseases.

Cambridge, MA, USA - June 28, 2022: Exterior view of the Alnylam headquarters in Cambridge, Massachusetts. Alnylam Pharmaceuticals, Inc. is an American biotechnology company focused on the discovery, development and commercialization of RNA interference (RNAi) therapeutics for genetically defined diseases.

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Alnylam’s Amvuttra reduced the risk of all-cause death or recurrent cardiovascular events by at least 28% in patients with transthyretin amyloidosis with cardiomyopathy, the company announced Monday.

Pictured: Alnylam’s headquarters building in Massachusetts/iStock, hapabapa

Alnylam Pharmaceuticals on Monday revealed topline data from the Phase III HELIOS-B study, showing that its RNAi therapy Amuvttra (vutrisiran) can significantly lower the risk of death and recurrent cardiovascular events in transthyretin amyloidosis patients with cardiomyopathy.

Alnylam CMO Pushkal Garg in a statement said the company is “thrilled” by the “overwhelmingly positive data” from HELIOS-B, which point to the potential of Amvuttra to be an effective treatment option for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). “The results showed that vutrisiran improved cardiovascular outcomes” as well as survival and quality of life in patients, according to Garg.

“We are moving with urgency to file these compelling data with regulators,” Garg said. Alnylam is looking to submit its global regulatory applications—including a supplemental New Drug Application with the FDA—later this year. The company has also submitted these data as a late-breaking abstract to the European Society of Cardiology for presentation at its upcoming medical meeting.

HELIOS-B is a randomized, double-blinded and placebo-controlled study that enrolled 655 ATTR-CM patients. During a double-blind period lasting up to 36 months, patients were given a 25-mg subcutaneous dose of Amvuttra or placebo once every three months. Eligible patients still on the study were then allowed to receive Amvuttra during an open-label extension period.

At the study’s baseline, some of the patients were being treated with Pfizer’s Vyndamax (tafamidis), an FDA-approved oral therapy for ATTR-CM. In these patients, Amvuttra reduced the risk of all-cause mortality and recurrent cardiovascular events by 28%. In those who were being treated with only Amvuttra, risk reduction for the composite endpoint was 33%.

Alnylam’s RNAi therapy also aced key secondary endpoints. Death from all causes was lowered by 36% in patients with Vyndamax exposure at baseline, and by 35% in patients treated with Amvuttra monotherapy.

Amvuttra, whether as a monotherapy or in the overall patient population, also significantly improved six-minute walk distance and New York Heart Association classification, among other measures of disease progression.

Designed to be administered as a subcutaneous injection, Amvuttra is a small-interfering RNA therapeutic that targets both mutant and wild-type transthyretin mRNA, tagging it for degradation. Amvuttra lowers serum levels of the transthyretin protein and counters the accumulation of its misfolded forms across the body, including the heart, helping to address the underlying pathological pathway in ATTR-CM.

Stifel analysts in a Monday note to investors said they believe the topline HELIOS-B data “are highly positive and support vutrisiran becoming a blockbuster in TTR-cardiomyopathy,” adding that “what stands out the most is the highly robust benefit on top of tafamidis.”

The FDA first approved Amvuttra in June 2022 for the treatment of ATTR amyloidosis with polyneuropathy—a similar condition where the misfolded transthyretin proteins afflict the nerves instead of the heart.

If the FDA approves its label expansion, Amvuttra would help Alnylam recoup from the regulator’s rejection in October 2023 blocking the use of Onpattro (patisiran) in ATTR-CM. The regulator at the time said that Alnylam had not sufficiently established the benefit of the siRNA therapy in ATTR-CM.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
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